In contrast to previous studies of diabetic neutrophils in vitro which reported phagocytic depression, RES hyperphagocytsis of colloidal carbon particles was observed in rats at 14 days after diabetes induction with streptozotocin (STZ). The carbon clearance half-time was significantly enhanced to 6.3 plus or minus 0.79 min compared to the citrate control group (12.7 plus or minus 9.98 min). Daily insulin replacement reversed the enhanced phagocytosis. Mechanisms proposed to explain RES hyperphagocytosis in diabetic animals include 1) hyperplasic of hepatic Kupffer cells, 2) endocrine imbalance, i.e., hypoinsulinemia and hyperglucagonemia, 3) enhanced phagocytic receptor activity, 4) elevation of plasma opsonic factor of fibronectin. The two pancreatic hormones, insulin and glucagon, have implicated as hepatotrophic factors for the regenerating liver. The inability to demonstrate hyperinsulinemia in initially well-fed rats is related to the reduction of liver glycogen and, therefore, plasma glucose sustaining reserves in partially hepatectomized rats compared to surgical sham controls. In rats fasted for 24 hr prior to 67% hepatectomy in order to deplete hepatic glycogen, basal portal venous hyperinsulinemia and hyperglucagonemia were noted suggesting enhanced pancreatic secretion of the two hormones. The evidence also implies that hepatic extraction and, therefore, cell membrane receptor binding of both insulin and glucagon by regenerating livers were enhanced even though portal venous levels of the two hormones were elevated.